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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Thymoquinone: A Review on its Pharmacological Importance, and its Association with Oxidative Stress, COVID-19, and Radiotherapy

Author(s): Seyithan Taysi*, Firas Shawqi Algburi, Zaid Rakan Mohammed, Omeed Akbar Ali and Muhammed Enes Taysi

Volume 22, Issue 14, 2022

Published on: 21 April, 2022

Page: [1847 - 1875] Pages: 29

DOI: 10.2174/1389557522666220104151225

Price: $65

Open Access Journals Promotions 2
Abstract

Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems, such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties, such as antioxidant, anti-inflammatory, antiviral, and antineoplastic. Its chemical structure indicates antiviral potential against many viruses, including the hepatitis C virus, human immunodeficiency virus, and other coronavirus diseases. Interestingly, molecular docking studies have demonstrated that TQ can potentially inhibit the development of the coronavirus disease 2019 (COVID-19) by binding to the receptor site on the transmembrane serine protease 2 (the activator enzyme that attaches the virus to the cell). In addition, TQ has been shown to be effective against cancer cells due to its inhibitory effect by binding to the different regions of MDM2, according to the proposed molecular docking study. Detailed in this review is the origin of TQ, its significance in alternative medicine, pharmacological value, potential as a cancer antiproliferative agent, use against the coronavirus disease 2019 (COVID-19) and for treatment of other diseases.

Keywords: Thymoquinone, oxidative, complementary medicine, therapeutic benefits, irradiation, coronavirus disease 2019, molecular docking study.

Graphical Abstract
[1]
Altay, H.; Demir, E.; Binici, H.; Aytac, I.; Taysi, M.E.; Taysi, S. Radioprotective effects of propolis and caffeic acid phenethyl ester on the tongue-tissues of total-head irradiated rats. Eur. J. Ther., 2020, 26(3), 202-207.
[2]
Roy, P.S.; Saikia, B.J. Cancer and cure: A critical analysis. Indian J. Cancer, 2016, 53(3), 441-442.
[http://dx.doi.org/10.5152/EurJTher.2020.19047] [PMID: 28244479]
[3]
Mirza, A.Z. Advancement in the development of heterocyclic nucleosides for the treatment of cancer - A review. Nucleosides Nucleotides Nucleic Acids, 2019, 38(11), 836-857.
[http://dx.doi.org/10.1080/15257770.2019.1615623] [PMID: 31135268]
[4]
Bakan, E.; Taysi, S.; Polat, M.F.; Dalga, S.; Umudum, Z.; Bakan, N.; Gumus, M. Nitric oxide levels and lipid peroxidation in plasma of patients with gastric cancer. Jpn. J. Clin. Oncol., 2002, 32(5), 162-166.
[http://dx.doi.org/10.1093/jjco/hyf035] [PMID: 12110642]
[5]
Mäbert, K.; Cojoc, M.; Peitzsch, C.; Kurth, I.; Souchelnytskyi, S.; Dubrovska, A. Cancer biomarker discovery: Current status and future perspectives. Int. J. Radiat. Biol., 2014, 90(8), 659-677.
[http://dx.doi.org/10.3109/09553002.2014.892229] [PMID: 24524284]
[6]
Polat, M.F.; Taysi, S.; Gul, M.; Cikman, O.; Yilmaz, I.; Bakan, E.; Erdogan, F. Oxidant/antioxidant status in blood of patients with malig-nant breast tumour and benign breast disease. Cell Biochem. Funct., 2002, 20(4), 327-331.
[http://dx.doi.org/10.1002/cbf.980] [PMID: 12415567]
[7]
Khayyo, N.; Taysi, M.E.; Demir, E.; Ulusal, H.; Cinar, K.; Tarakcioglu, M.; Taysi, S. Radioprotective effect of caffeic acid phenethyl ester on the brain tissue in rats who underwent total-head irradiation. Eur. J. Ther., 2019, 25(4), 265-272.
[http://dx.doi.org/10.5152/EurJTher.2019.18052]
[8]
Taysi, S.; Koc, M. Büyükokuroğlu, M.E.; Altinkaynak, K.; Sahin, Y.N. Melatonin reduces lipid peroxidation and nitric oxide during irra-diation-induced oxidative injury in the rat liver. J. Pineal Res., 2003, 34(3), 173-177.
[http://dx.doi.org/10.1034/j.1600-079X.2003.00024.x] [PMID: 12614476]
[9]
Koc, M.; Taysi, S.; Buyukokuroglu, M.E.; Bakan, N. Melatonin protects rat liver against irradiation-induced oxidative injury. J. Radiat. Res. (Tokyo), 2003, 44(3), 211-215.
[http://dx.doi.org/10.1269/jrr.44.211] [PMID: 14646223]
[10]
Koc, M.; Taysi, S.; Sezen, O.; Bakan, N. Levels of some acute-phase proteins in the serum of patients with cancer during radiotherapy. Biol. Pharm. Bull., 2003, 26(10), 1494-1497.
[http://dx.doi.org/10.1248/bpb.26.1494] [PMID: 14519962]
[11]
Emin Büyükokuroğlu, M.; Taysi, S.; Koç, M.; Bakan, N. Dantrolene protects erythrocytes against oxidative stress during whole-body irradiation in rats. Cell Biochem. Funct., 2003, 21(2), 127-131.
[http://dx.doi.org/10.1002/cbf.1008] [PMID: 12736901]
[12]
Karslioglu, I.; Ertekin, M.V.; Koçer, I.; Taysi, S.; Sezen, O.; Gepdiremen, A.; Balci, E. Protective role of intramuscularly administered vitamin E on the levels of lipid peroxidation and the activities of antioxidant enzymes in the lens of rats made cataractous with gamma-irradiation. Eur. J. Ophthalmol., 2004, 14(6), 478-485.
[http://dx.doi.org/10.1177/112067210401400606] [PMID: 15638096]
[13]
Ertekin, M.V.; Koçer, I. Karslioğlu, I.; Taysi, S.; Gepdiremen, A.; Sezen, O.; Balci, E.; Bakan, N. Effects of oral Ginkgo biloba supple-mentation on cataract formation and oxidative stress occurring in lenses of rats exposed to total cranium radiotherapy. Jpn. J. Ophthalmol., 2004, 48(5), 499-502.
[http://dx.doi.org/10.1007/s10384-004-0101-z] [PMID: 15486777]
[14]
Demir, E.; Taysi, S.; Ulusal, H.; Kaplan, D.S.; Cinar, K.; Tarakcioglu, M. Nigella sativa oil and thymoquinone reduce oxidative stress in the brain tissue of rats exposed to total head irradiation. Int. J. Radiat. Biol., 2020, 96(2), 228-235.
[http://dx.doi.org/10.1080/09553002.2020.1683636] [PMID: 31638880]
[15]
Akyuz, M.; Taysi, S.; Baysal, E.; Demir, E.; Alkis, H.; Akan, M.; Binici, H.; Karatas, Z.A. Radioprotective effect of thymoquinone on salivary gland of rats exposed to total cranial irradiation. Head Neck, 2017, 39(10), 2027-2035.
[http://dx.doi.org/10.1002/hed.24861] [PMID: 28708300]
[16]
Demir, E.; Taysi, S.; Al, B.; Demir, T.; Okumus, S.; Saygili, O.; Saricicek, E.; Dirier, A.; Akan, M.; Tarakcioglu, M.; Bagci, C. The effects of Nigella sativa oil, thymoquinone, propolis, and caffeic acid phenethyl ester on radiation-induced cataract. Wien. Klin. Wochenschr., 2016, 128(Suppl. 8), 587-595.
[http://dx.doi.org/10.1007/s00508-015-0736-4] [PMID: 25860848]
[17]
Prasanna, P.G.; Rawojc, K.; Guha, C.; Buchsbaum, J.C.; Miszczyk, J.U.; Coleman, C.N. Normal tissue injury induced by photon and pro-ton therapies: Gaps and opportunities. Int. J. Radiat. Oncol. Biol. Phys., 2021, 110(5), 1325-1340.
[http://dx.doi.org/10.1016/j.ijrobp.2021.02.043] [PMID: 33640423]
[18]
Karslioglu, I.; Ertekin, M.V.; Taysi, S.; Koçer, I.; Sezen, O.; Gepdiremen, A.; Koç, M.; Bakan, N. Radioprotective effects of melatonin on radiation-induced cataract. J. Radiat. Res. (Tokyo), 2005, 46(2), 277-282.
[http://dx.doi.org/10.1269/jrr.46.277] [PMID: 15988147]
[19]
Kocer, I.; Taysi, S.; Ertekin, M.V.; Karslioglu, I.; Gepdiremen, A.; Sezen, O.; Serifoglu, K. The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: A rat model. Graefes Arch. Clin. Exp. Ophthalmol., 2007, 245(4), 588-594.
[http://dx.doi.org/10.1007/s00417-005-0097-1] [PMID: 16915402]
[20]
Taysi, S.; Okumus, S.; Ezirmik, S.; Uzun, N.; Yilmaz, A.; Akyuz, M.; Tekelioglu, U.; Dirier, A.; Al, B. The protective effects of L-carnitine and vitamin E in rat lenses in irradiation-induced oxidative injury. Adv. Clin. Exp. Med., 2011, 20(1), 15-21.
[21]
Hosseinimehr, S.J. Trends in the development of radioprotective agents. Drug Discov. Today, 2007, 12(19-20), 794-805.
[http://dx.doi.org/10.1016/j.drudis.2007.07.017] [PMID: 17933679]
[22]
Taysi, S.; Alafandi, N.; Demir, E.; Çinar, K. Propolis attenuates nitrosative stress in the brain tissue of rats exposed to total head irradia-tion. Eur. J. Ther., 2021, 69(5), 362-367.
[23]
Cikman, O.; Taysi, S.; Gulsen, M.T.; Demir, E.; Akan, M.; Diril, H.; Kiraz, H.A.; Karaayvaz, M.; Tarakcioglu, M. The Radioprotective effects of caffeic acid phenethyl ester and thymoquinone on oxidative and nitrosative stress in liver tissue of rats exposed to total head irradiation. West Indian Med. J., 2015, 65(1), 1-7.
[PMID: 26716794]
[24]
Cikman, O.; Taysi, S.; Gulsen, M.T.; Demir, E.; Akan, M.; Diril, H.; Kiraz, H.A.; Karaayvaz, M.; Tarakcioglu, M. The radio-protective effects of caffeic acid phenethyl ester and thymoquinone in rats exposed to total head irradiation. Wien. Klin. Wochenschr., 2015, 127(3-4), 103-108.
[http://dx.doi.org/10.1007/s00508-014-0635-0] [PMID: 25409943]
[25]
Alkis, H.E.; Kuzhan, A.; Dirier, A.; Tarakcioglu, M.; Demir, E.; Saricicek, E.; Demir, T.; Ahlatci, A.; Demirci, A.; Cinar, K.; Taysi, S. Neu-roprotective effects of propolis and Caffeic Acid Phenethyl Ester (CAPE) on the radiation-injured brain tissue (Neuroprotective effects of propolis and CAPE). Int J Radiat Res, 2015, 13(4), 297-303.
[26]
Taysi, S.; Baysal, E.; Demir, E.; Akan, M.; Binici, H.; Adli, M.; Akyuz, M.; Saricicek, E.; Kara, F.; Ulusal, H.; Karataslioglu, E. Thymo-quinone reduces oxidative and nitrosative stress in tongue-tissue of rats exposed to total cranial irradiation. West Indian Med. J., 2016, 65(3), 543-550.
[27]
Sürmelioğlu, D.; Gündoğar, H.; Taysi, S.; Bağiş, Y.H. Effect of different bleaching techniques on DNA damage biomarkers in serum, sali-va, and GCF. Hum. Exp. Toxicol., 2021, 40(8), 1332-1341.
[http://dx.doi.org/10.1177/0960327121996030] [PMID: 33622079]
[28]
Ahlatci, A.; Kuzhan, A.; Taysi, S.; Demirtas, O.C.; Alkis, H.E.; Tarakcioglu, M.; Demirci, A.; Caglayan, D.; Saricicek, E.; Cinar, K. Radia-tion-modifying abilities of Nigella sativa and thymoquinone on radiation-induced nitrosative stress in the brain tissue. Phytomedicine, 2014, 21(5), 740-744.
[http://dx.doi.org/10.1016/j.phymed.2013.10.023] [PMID: 24268807]
[29]
Üstün, K. Taysı, S.; Sezer, U.; Demir, E.; Baysal, E.; Demir, T.; Sarıçiçek, E.; Alkış, H.; Senyurt, S.Z.; Tarakçıoğlu, M.; Aksoy, N. Radio-protective effects of Nigella sativa oil on oxidative stress in tongue tissue of rats. Oral Dis., 2014, 20(1), 109-113.
[http://dx.doi.org/10.1111/odi.12082] [PMID: 23444976]
[30]
Group., I. D. A. Update of mortality attributable to diabetes for the IDF Diabetes Atlas: estimates for the year 2011. Diabetes Res. Clin. Pract., 2013, 100, 277-279.
[PMID: 23506763]
[31]
Cikman, O.; Ozkan, A.; Aras, A.B.; Soylemez, O.; Alkis, H.; Taysi, S.; Karaayvaz, M. Radioprotective effects of Nigella sativa oil against oxidative stress in liver tissue of rats exposed to total head irradiation. J. Invest. Surg., 2014, 27(5), 262-266.
[http://dx.doi.org/10.3109/08941939.2014.898811] [PMID: 24679182]
[32]
Taysi, S.; Tascan, A.S.; Ugur, M.G.; Demir, M. Radicals, oxidative/nitrosative stress and preeclampsia. Mini Rev. Med. Chem., 2019, 19(3), 178-193.
[http://dx.doi.org/10.2174/1389557518666181015151350] [PMID: 30324879]
[33]
Ercan, K.; Gecesefa, O.F.; Taysi, M.E.; Ali Ali, O.A.; Taysi, S. Moringa oleifera: A review of its occurrence, pharmacological importance and oxidative stress. Mini Rev. Med. Chem., 2021, 21(3), 380-396.
[http://dx.doi.org/10.2174/1389557520999200728162453] [PMID: 32723270]
[34]
Celik, E.; Taysi, S.; Sucu, S.; Ulusal, H.; Sevincler, E.; Celik, A. Urotensin 2 and oxidative stress levels in maternal serum in pregnancies complicated by intrauterine growth restriction. Medicina (Kaunas), 2019, 55(7), E328.
[http://dx.doi.org/10.3390/medicina55070328] [PMID: 31269637]
[35]
Baysal, E.; Gulsen, S.; Aytac, I.; Celenk, F.; Ensari, N.; Taysi, S.; Binici, H.; Durucu, C.; Mumbuc, S.; Kanlikama, M. Oxidative stress in otosclerosis. Redox Rep., 2017, 22(5), 235-239.
[http://dx.doi.org/10.1080/13510002.2016.1207920] [PMID: 27387094]
[36]
Taysi, S.; Okumus, S.; Akyuz, M.; Uzun, N.; Aksoy, A.; Demir, E.; Orkmez, M.; Tarakcioglu, M.; Adli, M. Zinc administration modulates radiation-induced oxidative injury in lens of rat. Pharmacogn. Mag., 2012, 8(32), 245-249.
[http://dx.doi.org/10.4103/0973-1296.103646] [PMID: 24082625]
[37]
Okumus, S.; Taysi, S.; Orkmez, M.; Saricicek, E.; Demir, E.; Adli, M.; Al, B. The effects of oral Ginkgo biloba supplementation on radia-tion-induced oxidative injury in the lens of rat. Pharmacogn. Mag., 2011, 7(26), 141-145.
[http://dx.doi.org/10.4103/0973-1296.80673] [PMID: 21716624]
[38]
Taysi, S.; Memisogullari, R.; Koc, M.; Yazici, A.T.; Aslankurt, M.; Gumustekin, K.; Al, B.; Ozabacigil, F.; Yilmaz, A.; Tahsin Ozder, H. Melatonin reduces oxidative stress in the rat lens due to radiation-induced oxidative injury. Int. J. Radiat. Biol., 2008, 84(10), 803-808.
[http://dx.doi.org/10.1080/09553000802390932] [PMID: 18979314]
[39]
Taysi, S.; Cikman, O.; Kaya, A.; Demircan, B.; Gumustekin, K.; Yilmaz, A.; Boyuk, A.; Keles, M.; Akyuz, M.; Turkeli, M. Increased oxi-dant stress and decreased antioxidant status in erythrocytes of rats fed with zinc-deficient diet. Biol. Trace Elem. Res., 2008, 123(1-3), 161-167.
[http://dx.doi.org/10.1007/s12011-008-8095-x] [PMID: 18273565]
[40]
Kalyoncu, Ş, Yilmaz, B.; Demir, M.; Tuncer, M.; Bozdağ, Z.; Ince, O.; Bozdayi, M.A.; Ulusal, H.; Taysi, S. Melatonin attenuates ovarian ischemia reperfusion injury in rats by decreasing oxidative stress index and peroxynitrite. Turk. J. Med. Sci., 2020, 50(6), 1513-1522.
[http://dx.doi.org/10.3906/sag-2004-135] [PMID: 32927928]
[41]
Kalyoncu, S.; Yilmaz, B.; Demir, M.; Tuncer, M.; Bozdag, Z.; Ince, O.; Akif Bozdayi, M.; Ulusal, H.; Taysi, S. Octreotide and lanreotide decrease ovarian ischemia-reperfusion injury in rats by improving oxidative and nitrosative stress. J. Obstet. Gynaecol. Res., 2020, 46(10), 2050-2058.
[http://dx.doi.org/10.1111/jog.14379] [PMID: 32748523]
[42]
Akinci, S.; Özcan, H.C.; Balat, Ö. Uğur, M.G.; Öztürk, E.; Taysi, S.; Sucu, S. Assessment of β-hydroxydeoxyguanosine levels in patients with preeclampsia: A prospective study. Clin. Exp. Obstet. Gynecol., 2017, 44(2), 226-229.
[PMID: 29746027]
[43]
Sezer, U. Şenyurt, S.Z.; Gündoğar, H.; Erciyas, K.; Üstün, K.; Kimyon, G.; Kırtak, N.; Taysı, S.; Onat, A.M. Effect of chronic periodontitis on oxidative status in patients with psoriasis and psoriatic arthritis. J. Periodontol., 2016, 87(5), 557-565.
[http://dx.doi.org/10.1902/jop.2015.150337] [PMID: 26693694]
[44]
Geyik, S. Altunısık, E.; Neyal, A.M.; Taysi, S. Oxidative stress and DNA damage in patients with migraine. J. Headache Pain, 2016, 17, 10.
[http://dx.doi.org/10.1186/s10194-016-0606-0] [PMID: 26883365]
[45]
Alici, D.; Bulbul, F.; Virit, O.; Unal, A.; Altindag, A.; Alpak, G.; Alici, H.; Ermis, B.; Orkmez, M.; Taysi, S.; Savas, H. Evaluation of oxida-tive metabolism and oxidative DNA damage in patients with obsessive-compulsive disorder. Psychiatry Clin. Neurosci., 2016, 70(2), 109-115.
[http://dx.doi.org/10.1111/pcn.12362] [PMID: 26388322]
[46]
Taysi, S.; Gul, M.; Sari, R.A.; Akcay, F.; Bakan, N. Serum oxidant/antioxidant status of patients with systemic lupus erythematosus. Clin. Chem. Lab. Med., 2002, 40(7), 684-688.
[http://dx.doi.org/10.1515/CCLM.2002.117] [PMID: 12241014]
[47]
Taysi, S.; Kocer, I.; Memisogullari, R.; Kiziltunc, A. Serum oxidant/antioxidant status in patients with Behçet’s disease. Ann. Clin. Lab. Sci., 2002, 32(4), 377-382.
[PMID: 12458889]
[48]
Büyükokuroğlu, M.E.; Taysi, S.; Polat, F.; Göçer, F. Mechanism of the beneficial effects of dantrolene sodium on ethanol-induced acute gastric mucosal injury in rats. Pharmacol. Res., 2002, 45(5), 421-425.
[http://dx.doi.org/10.1006/phrs.2002.0951] [PMID: 12123631]
[49]
Taysi, S.; Gumustekin, K.; Demircan, B.; Aktas, O.; Oztasan, N.; Akcay, F.; Suleyman, H.; Akar, S.; Dane, S.; Gul, M. Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver. Pharm. Biol., 2010, 48(5), 488-493.
[http://dx.doi.org/10.3109/13880200903179707] [PMID: 20645788]
[50]
Gumustekin, K.; Taysi, S.; Alp, H.H.; Aktas, O.; Oztasan, N.; Akcay, F.; Suleyman, H.; Akar, S.; Dane, S.; Gul, M. Vitamin E and Hip-pophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart. Cell Biochem. Funct., 2010, 28(4), 329-333.
[http://dx.doi.org/10.1002/cbf.1663] [PMID: 20517898]
[51]
Uslu, C.; Taysi, S.; Bakan, N. Lipid peroxidation and antioxidant enzyme activities in experimental maxillary sinusitis. Ann. Clin. Lab. Sci., 2003, 33(1), 18-22.
[PMID: 12661894]
[52]
Gul, M.; Demircan, B.; Taysi, S.; Oztasan, N.; Gumustekin, K.; Siktar, E.; Polat, M.F.; Akar, S.; Akcay, F.; Dane, S. Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart. Comp. Biochem. Physiol. A Mol. Integr. Physiol., 2006, 143(2), 239-245.
[http://dx.doi.org/10.1016/j.cbpa.2005.12.001] [PMID: 16426880]
[53]
Sies, H.; Berndt, C.; Jones, D.P. Oxidative stress. Annu. Rev. Biochem., 2017, 86, 715-748.
[http://dx.doi.org/10.1146/annurev-biochem-061516-045037] [PMID: 28441057]
[54]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[55]
Giles, G.I.; Tasker, K.M.; Jacob, C. Hypothesis: The role of reactive sulfur species in oxidative stress. Free Radic. Biol. Med., 2001, 31(10), 1279-1283.
[http://dx.doi.org/10.1016/S0891-5849(01)00710-9] [PMID: 11705707]
[56]
DeLeon, E.R.; Gao, Y.; Huang, E.; Arif, M.; Arora, N.; Divietro, A.; Patel, S.; Olson, K.R. A case of mistaken identity: Are reactive oxygen species actually reactive sulfide species? Am. J. Physiol. Regul. Integr. Comp. Physiol., 2016, 310(7), R549-R560.
[http://dx.doi.org/10.1152/ajpregu.00455.2015] [PMID: 26764057]
[57]
Poole, L.B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med., 2015, 80, 148-157.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.11.013] [PMID: 25433365]
[58]
Sies, H. Biochemistry of oxidative stress. Angew. Chem. Int. Ed. Engl., 1986, 25(12), 1058-1071.
[http://dx.doi.org/10.1002/anie.198610581]
[59]
Labunskyy, V.M.; Hatfield, D.L.; Gladyshev, V.N. Selenoproteins: Molecular pathways and physiological roles. Physiol. Rev., 2014, 94(3), 739-777.
[http://dx.doi.org/10.1152/physrev.00039.2013] [PMID: 24987004]
[60]
Sies, H. Oxidative stress: Concept and some practical aspects. Antioxidants, 2020, 9(9), E852.
[http://dx.doi.org/10.3390/antiox9090852] [PMID: 32927924]
[61]
Pompella, A.; Sies, H.; Wacker, R.; Brouns, F.; Grune, T.; Biesalski, H.K.; Frank, J. The use of total antioxidant capacity as surrogate mar-ker for food quality and its effect on health is to be discouraged. Nutrition, 2014, 30(7-8), 791-793.
[http://dx.doi.org/10.1016/j.nut.2013.12.002] [PMID: 24984994]
[62]
Sies, H. Total antioxidant capacity: Appraisal of a concept. J. Nutr., 2007, 137(6), 1493-1495.
[http://dx.doi.org/10.1093/jn/137.6.1493] [PMID: 17513413]
[63]
Wayner, D.D.; Burton, G.W.; Ingold, K.U.; Locke, S. Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. The important contribution made by plasma proteins. FEBS Lett., 1985, 187(1), 33-37.
[http://dx.doi.org/10.1016/0014-5793(85)81208-4] [PMID: 4018255]
[64]
Bartosz, G. Non-enzymatic antioxidant capacity assays: Limitations of use in biomedicine. Free Radic. Res., 2010, 44(7), 711-720.
[http://dx.doi.org/10.3109/10715761003758114] [PMID: 20446897]
[65]
Demir, M.; Yilmaz, B.; Kalyoncu, S.; Tuncer, M.; Bozdag, Z.; Ince, O.; Bozdayi, M.A.; Ulusal, H.; Taysi, S. Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative/nitrosative stress. Taiwan. J. Obstet. Gynecol., 2021, 60(1), 45-50.
[http://dx.doi.org/10.1016/j.tjog.2020.10.004] [PMID: 33495007]
[66]
Memisoğullari, R.; Taysi, S.; Bakan, E.; Capoglu, I. Antioxidant status and lipid peroxidation in type II diabetes mellitus. Cell Biochem. Funct., 2003, 21(3), 291-296.
[http://dx.doi.org/10.1002/cbf.1025] [PMID: 12910484]
[67]
Aksoy, H.; Taysi, S.; Altinkaynak, K.; Bakan, E.; Bakan, N.; Kumtepe, Y. Antioxidant potential and transferrin, ceruloplasmin, and lipid peroxidation levels in women with preeclampsia. J. Investig. Med., 2003, 51(5), 284-287.
[http://dx.doi.org/10.1136/jim-51-05-15] [PMID: 14577518]
[68]
Baysal, E.; Taysi, S.; Aksoy, N.; Uyar, M.; Celenk, F.; Karatas, Z.A.; Tarakcioglu, M.; Bilinç, H.; Mumbuç, S.; Kanlikama, M. Serum pa-raoxonase, arylesterase activity and oxidative status in patients with Obstructive Sleep Apnea Syndrome (OSAS). Eur. Rev. Med. Pharmacol. Sci., 2012, 16(6), 770-774.
[PMID: 22913209]
[69]
Baysal, E.; Aksoy, N.; Kara, F.; Taysi, S. Taşkın, A.; Bilinç, H.; Cevik, C.; Celenk, F.; Kanlıkama, M. Oxidative stress in chronic otitis media. Eur. Arch. Otorhinolaryngol., 2013, 270(4), 1203-1208.
[http://dx.doi.org/10.1007/s00405-012-2070-z] [PMID: 22711004]
[70]
Finley, J.W.; Kong, A.N.; Hintze, K.J.; Jeffery, E.H.; Ji, L.L.; Lei, X.G. Antioxidants in foods: state of the science important to the food industry. J. Agric. Food Chem., 2011, 59(13), 6837-6846.
[http://dx.doi.org/10.1021/jf2013875] [PMID: 21627162]
[71]
Berger, R.G.; Lunkenbein, S.; Ströhle, A.; Hahn, A. Antioxidants in food: Mere myth or magic medicine? Crit. Rev. Food Sci. Nutr., 2012, 52(2), 162-171.
[http://dx.doi.org/10.1080/10408398.2010.499481] [PMID: 22059961]
[72]
Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr., 2005, 81(1)(Suppl.), 230S-242S.
[http://dx.doi.org/10.1093/ajcn/81.1.230S] [PMID: 15640486]
[73]
Makahleh, A.; Saad, B.; Bari, M. Synthetic phenolics as antioxidants for food preservation. In: Handbook of Antioxidants for Food Preser-vation; Fereidoon, S., Ed.; Elsevier: Amsterdam, 2015, pp. 51-78.
[http://dx.doi.org/10.1016/B978-1-78242-089-7.00003-8]
[74]
Dolatabadi, J.E.N.; Kashanian, S. A review on DNA interaction with synthetic phenolic food additives. Food Res. Int., 2010, 43(5), 1223-1230.
[http://dx.doi.org/10.1016/j.foodres.2010.03.026]
[75]
Kancheva, V.D. Phenolic antioxidants-radical‐scavenging and chain‐breaking activity: A comparative study. Eur. J. Lipid Sci. Technol., 2009, 111(11), 1072-1089.
[http://dx.doi.org/10.1002/ejlt.200900005]
[76]
Rock, C.L.; Jacob, R.A.; Bowen, P.E. Update on the biological characteristics of the antioxidant micronutrients: Vitamin C, vitamin E, and the carotenoids. J. Am. Diet. Assoc., 1996, 96(7), 693-702.
[http://dx.doi.org/10.1016/S0002-8223(96)00190-3] [PMID: 8675913]
[77]
Park, S.H.; Kim, M.; Lee, S.; Jung, W.; Kim, B. Therapeutic potential of natural products in treatment of cervical cancer: A review. Nutrients, 2021, 13(1), E154.
[http://dx.doi.org/10.3390/nu13010154] [PMID: 33466408]
[78]
Ezzat, S.M.; Shouman, S.A.; Elkhoely, A.; Attia, Y.M.; Elsesy, M.S.; El Senousy, A.S.; Choucry, M.A.; El Gayed, S.H.; El Sayed, A.A.; Sattar, E.A.; El Tanbouly, N. Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars. Sci. Rep., 2018, 8(1), 544.
[http://dx.doi.org/10.1038/s41598-017-18944-0] [PMID: 29323210]
[79]
Aslan, R.; Borazan, S. Siyah Reçete: Çörek Otu (Nigella sativa). Ayrinti Dergisi, 2019, 7(74), 41-47.
[80]
Ragaa, M.S. Clinical and therapeutic trials of Nigella sativa. Turk Silahli Kuvvetleri Koruyucu Hekim. Bul., 2010, 9(5), 213-522.
[81]
Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Damanhouri, Z.A.; Anwar, F. A review on therapeutic po-tential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3(5), 337-352.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[82]
Khare, C.P. Encyclopedia of Indian Medicinal Plants; Springes-Verlag Berlin Heidelberg: NewYork, 2010.
[83]
Ali, B.; Blunden, G. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res., 2003, 17(4), 299-305.
[84]
Entok, E.; Ustuner, M.C.; Ozbayer, C.; Tekin, N.; Akyuz, F.; Yangi, B.; Kurt, H.; Degirmenci, I.; Gunes, H.V. Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation. Mol. Biol. Rep., 2014, 41(5), 2827-2834.
[http://dx.doi.org/10.1007/s11033-014-3137-2] [PMID: 24474661]
[85]
Soleimani, H.; Ranjbar, A.; Baeeri, M.; Mohammadirad, A.; Khorasani, R.; Yasa, N.; Abdollahi, M. Rat plasma oxidation status after Ni-gella sativa L. botanical treatment in CCL4-treated rats. Toxicol. Mech. Methods, 2008, 18(9), 725-731.
[http://dx.doi.org/10.1080/15376510802232233] [PMID: 20020931]
[86]
Ashraf, S.S.; Rao, M.V.; Kaneez, F.S.; Qadri, S.; Al-Marzouqi, A.H.; Chandranath, I.S.; Adem, A. Nigella sativa extract as a potent anti-oxidant for petrochemical-induced oxidative stress. J. Chromatogr. Sci., 2011, 49(4), 321-326.
[http://dx.doi.org/10.1093/chrsci/49.4.321] [PMID: 21439125]
[87]
Bakathir, H.A.; Abbas, N.A. Detection of the antibacterial effect of Nigella sativa ground seeds with water. Afr. J. Tradit. Complement. Altern. Med., 2011, 8(2), 159-164.
[http://dx.doi.org/10.4314/ajtcam.v8i2.63203] [PMID: 22238497]
[88]
Al-Suhaimi, E.A. Hepatoprotective and immunological functions of Nigella sativa seed oil against hypervitaminosis A in adult male rats. Int. J. Vitam. Nutr. Res., 2012, 82(4), 288-297.
[http://dx.doi.org/10.1024/0300-9831/a000121] [PMID: 23591666]
[89]
Talib, W.H.; Abukhader, M.M.W.; Abukhader, M. Combinatorial effects of thymoquinone on the anticancer activity and hepatotoxicity of the prodrug CB 1954. Sci. Pharm., 2013, 81(2), 519-530.
[http://dx.doi.org/10.3797/scipharm.1211-15] [PMID: 23833717]
[90]
Bourgou, S.; Ksouri, R.; Bellila, A.; Skandrani, I.; Falleh, H.; Marzouk, B. Phenolic composition and biological activities of Tunisian Ni-gella sativa L. shoots and roots. C. R. Biol., 2008, 331(1), 48-55.
[http://dx.doi.org/10.1016/j.crvi.2007.11.001] [PMID: 18187122]
[91]
Aikemu, A.; Xiaerfuding, X.; Shiwenhui, C.; Abudureyimu, M.; Maimaitiyiming, D. Immunomodulatory and anti-tumor effects of Nigella glandulifera freyn and sint seeds on ehrlich ascites carcinoma in mouse model. Pharmacogn. Mag., 2013, 9(35), 187-191.
[http://dx.doi.org/10.4103/0973-1296.113258] [PMID: 23929999]
[92]
Motaghed, M.; Al-Hassan, F.M.; Hamid, S.S. Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharmacognosy Res., 2013, 5(3), 200-206.
[http://dx.doi.org/10.4103/0974-8490.112428] [PMID: 23900121]
[93]
Ijaz, H.; Tulain, U.R.; Qureshi, J.; Danish, Z.; Musayab, S.; Akhtar, M.F.; Saleem, A.; Khan, K.K.; Zaman, M.; Waheed, I.; Khan, I.; Ab-del-Daim, M. Review: Nigella sativa (Prophetic Medicine): A Review. Pak. J. Pharm. Sci., 2017, 30(1), 229-234.
[PMID: 28603137]
[94]
Tariq, M. Nigella sativa seeds: Folklore treatment in modern day medicine. Saudi J. Gastroenterol., 2008, 14(3), 105-106.
[http://dx.doi.org/10.4103/1319-3767.41725] [PMID: 19568515]
[95]
Desai, S.D.; Shaik, H.S.; Kusal, K.D.; Haseena, S. Phytochemical analysis of Nigella sativa and it’s antidiabetic effect. J Pharm Sci Res, 2015, 7(8), 527-532.
[96]
Begum, S.; Mannan, A. A review on Nigella sativa: A marvel herb. J. Drug Deliv. Ther., 2020, 10(2), 213-219.
[http://dx.doi.org/10.22270/jddt.v10i2.3913]
[97]
Khare, C. Encyclopedia of Indian Medicinal Plants: Rational Western Therapy, Ayurvedic and Other Traditional Usage, Botany; Springer: Cham, 2004.
[98]
Hosseini, M.; Zakeri, S.; Khoshdast, S.; Yousefian, F.T.; Rastegar, M.; Vafaee, F.; Kahdouee, S.; Ghorbani, F.; Rakhshandeh, H.; Kazemi, S.A. The effects of Nigella sativa hydro-alcoholic extract and thymoquinone on lipopolysaccharide - induced depression like behavior in rats. J. Pharm. Bioallied Sci., 2012, 4(3), 219-225.
[http://dx.doi.org/10.4103/0975-7406.99052] [PMID: 22923964]
[99]
Rajsekhar, S.; Kuldeep, B. Pharmacognosy and pharmacology of Nigella sativa-A review. Int. Res. J. Pharm., 2011, 2(11), 36-39.
[100]
El–Dakhakhny, M. Studies on the chemical constitution of Egyptian Nigella sativa l. Seeds. (II1) the essential oil. Planta Med., 1963, 11(04), 465-470.
[http://dx.doi.org/10.1055/s-0028-1100266]
[101]
Gali-Muhtasib, H.U.; Abou Kheir, W.G.; Kheir, L.A.; Darwiche, N.; Crooks, P.A. Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes. Anticancer Drugs, 2004, 15(4), 389-399.
[http://dx.doi.org/10.1097/00001813-200404000-00012] [PMID: 15057144]
[102]
Darakhshan, S.; Bidmeshki Pour, A.; Hosseinzadeh Colagar, A.; Sisakhtnezhad, S. Thymoquinone and its therapeutic potentials. Pharmacol. Res., 2015, 95-96, 138-158.
[http://dx.doi.org/10.1016/j.phrs.2015.03.011] [PMID: 25829334]
[103]
el Tahir, K.E.; Ashour, M.M.; al-Harbi, M.M. The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen. Pharmacol., 1993, 24(5), 1115-1122.
[http://dx.doi.org/10.1016/0306-3623(93)90358-5] [PMID: 8270170]
[104]
Abdel-Fattah, A.M.; Matsumoto, K.; Watanabe, H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur. J. Pharmacol., 2000, 400(1), 89-97.
[http://dx.doi.org/10.1016/S0014-2999(00)00340-X] [PMID: 10913589]
[105]
Kahila, M.M.H.; Najy, A.M.; Rahaie, M.; Mir-Derikvand, M. Effect of nanoparticle treatment on expression of a key gene involved in thymoquinone biosynthetic pathway in Nigella sativa L. Nat. Prod. Res., 2018, 32(15), 1858-1862.
[http://dx.doi.org/10.1080/14786419.2017.1405398] [PMID: 29172688]
[106]
Salmani, J.M.; Asghar, S.; Lv, H.; Zhou, J. Aqueous solubility and degradation kinetics of the phytochemical anticancer thymoquinone; probing the effects of solvents, pH and light. Molecules, 2014, 19(5), 5925-5939.
[http://dx.doi.org/10.3390/molecules19055925] [PMID: 24815311]
[107]
Güzelsoy, P.; Aydin, S. Başaran, N. Çörek otunun (Nigella sativa L.) aktif bileşeni timokinonun İnsan sağlığı üzerine olası etkileri. J. Lit. Pharm. Sci., 2018, 7(2), 118-135.
[108]
Lupidi, G.; Scire, A.; Camaioni, E.; Khalife, K.H.; De Sanctis, G.; Tanfani, F.; Damiani, E. Thymoquinone, a potential therapeutic agent of Nigella sativa, binds to site I of human serum albumin. Phytomedicine, 2010, 17(10), 714-720.
[http://dx.doi.org/10.1016/j.phymed.2010.01.011] [PMID: 20171066]
[109]
Alhebshi, A.H.; Odawara, A.; Gotoh, M.; Suzuki, I. Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage. Neurosci. Lett., 2014, 570, 126-131.
[http://dx.doi.org/10.1016/j.neulet.2013.09.049] [PMID: 24080376]
[110]
Salem, M.L. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol., 2005, 5(13-14), 1749-1770.
[http://dx.doi.org/10.1016/j.intimp.2005.06.008] [PMID: 16275613]
[111]
Farooqui, Z.; Shahid, F.; Khan, A.A.; Khan, F. Oral administration of Nigella sativa oil and thymoquinone attenuates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney. Biomed. Pharmacother., 2017, 96, 912-923.
[http://dx.doi.org/10.1016/j.biopha.2017.12.007] [PMID: 29223554]
[112]
Yucel, A.; Sucu, M.; Al-Taesh, H.; Ulusal, H.; Midik Ertosun, F.; Taysi, S. Evaluation of oxidative DNA damage and thiol-disulfide ho-meostasis in patients with aortic valve sclerosis. Eur. J. Ther., 2021, 27(3), 241-24.
[http://dx.doi.org/10.5152/eurjther.2021.20123]
[113]
Khalife, K.H.; Lupidi, G. Nonenzymatic reduction of thymoquinone in physiological conditions. Free Radic. Res., 2007, 41(2), 153-161.
[http://dx.doi.org/10.1080/10715760600978815] [PMID: 17364941]
[114]
Gomathinayagam, R.; Ha, J.H.; Jayaraman, M.; Song, Y.S.; Isidoro, C.; Dhanasekaran, D.N. Chemopreventive and anticancer effects of thymoquinone: Cellular and molecular targets. J. Cancer Prev., 2020, 25(3), 136-151.
[http://dx.doi.org/10.15430/JCP.2020.25.3.136] [PMID: 33033708]
[115]
Khalife, K.H.; Lupidi, G. Reduction of hypervalent states of myoglobin and hemoglobin to their ferrous forms by thymoquinone: The role of GSH, NADH and NADPH. Biochim. Biophys. Acta, 2008, 1780(4), 627-637.
[http://dx.doi.org/10.1016/j.bbagen.2007.12.006] [PMID: 18206117]
[116]
Effenberger, K.; Breyer, S.; Schobert, R. Terpene conjugates of the Nigella sativa seed-oil constituent thymoquinone with enhanced effica-cy in cancer cells. Chem. Biodivers., 2010, 7(1), 129-139.
[http://dx.doi.org/10.1002/cbdv.200900328] [PMID: 20087986]
[117]
Badr, G.; Lefevre, E.A.; Mohany, M. Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis. PLoS One, 2011, 6(9), e23741.
[http://dx.doi.org/10.1371/journal.pone.0023741] [PMID: 21912642]
[118]
Gurung, R.L.; Lim, S.N.; Khaw, A.K.; Soon, J.F.; Shenoy, K.; Mohamed Ali, S.; Jayapal, M.; Sethu, S.; Baskar, R.; Hande, M.P. Thymo-quinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS One, 2010, 5(8), e12124.
[http://dx.doi.org/10.1371/journal.pone.0012124] [PMID: 20711342]
[119]
Velho-Pereira, R.; Kumar, A.; Pandey, B.N.; Jagtap, A.G.; Mishra, K.P. Radiosensitization in human breast carcinoma cells by thymoqui-none: Role of cell cycle and apoptosis. Cell Biol. Int., 2011, 35(10), 1025-1029.
[http://dx.doi.org/10.1042/CBI20100701] [PMID: 21557727]
[120]
Hussain, A.R.; Ahmed, M.; Ahmed, S.; Manogaran, P.; Platanias, L.C.; Alvi, S.N.; Al-Kuraya, K.S.; Uddin, S. Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma. Free Radic. Biol. Med., 2011, 50(8), 978-987.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.12.034] [PMID: 21215312]
[121]
El-Mahdy, M.A.; Zhu, Q.; Wang, Q.E.; Wani, G.; Wani, A.A. Thymoquinone induces apoptosis through activation of caspase-8 and mito-chondrial events in p53-null myeloblastic leukemia HL-60 cells. Int. J. Cancer, 2005, 117(3), 409-417.
[http://dx.doi.org/10.1002/ijc.21205] [PMID: 15906362]
[122]
Paramasivam, A.; Sambantham, S.; Shabnam, J.; Raghunandhakumar, S.; Anandan, B.; Rajiv, R.; Vijayashree Priyadharsini, J.; Jayaraman, G. Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP. Toxicol. Lett., 2012, 213(2), 151-159.
[http://dx.doi.org/10.1016/j.toxlet.2012.06.011] [PMID: 22732633]
[123]
Lei, X.; Lv, X.; Liu, M.; Yang, Z.; Ji, M.; Guo, X.; Dong, W. Thymoquinone inhibits growth and augments 5-fluorouracil-induced apopto-sis in gastric cancer cells both in vitro and in vivo. Biochem. Biophys. Res. Commun., 2012, 417(2), 864-868.
[http://dx.doi.org/10.1016/j.bbrc.2011.12.063] [PMID: 22206670]
[124]
Mansour, M.A.; Nagi, M.N.; El-Khatib, A.S.; Al-Bekairi, A.M. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxida-tion and DT-diaphorase in different tissues of mice: A possible mechanism of action. Cell Biochem. Funct., 2002, 20(2), 143-151.
[http://dx.doi.org/10.1002/cbf.968] [PMID: 11979510]
[125]
Algburi, F.S.; Al-Tikrity, N.Y.; Ali, O.A.; Taysi, S. Effect of a metformin derivative containing nitrile group on some biochemical variables in rabbits induced by alloxane. Ann. Rom. Soc. Cell Biol., 2021, 4726-4731.
[126]
Mohammed, R.O.; Abdul-Razzaq, F.S. Study of biochemistry and analytical of metformin as a suggested pro-drug for phosphoamide. Rafidain J. Sci., 2020, 29(1), 48-61.
[http://dx.doi.org/10.33899/rjs.2020.164474]
[127]
Al-Tikrity, N.Y.; Firas, S.; Beyatli, A. Preparation of nitrile derivative and study its effect as a possible novel drug for diabetes. Ann. Trop. Med. Health, 2020, 23, 516-542.
[http://dx.doi.org/10.36295/ASRO.2020.23734]
[128]
Razzak, F.S.A.; Al-Rubaei, Z.M.; Mohammed, Y.A-G. Synthesis of novel acetylinc derivative of metformin as a DPP-4 inhibitors and study its effects on sera of rabbits with induced diabetes. Synthesis, 2016, 6(8), 143-153.
[129]
Algburi, F.; Muhammed, J.M.; Mustafa, E.M. Synergistic effect of l-carnitine, omega-3 with metformin on the level of apelin-36 and some hormones in rabbits induced with diabetes. Asian J. Microbiol. Biotechnol. Environ. Sci., 2019, 21, 38-45.
[130]
Esposito, K.; Maiorino, M.I.; Bellastella, G.; Panagiotakos, D.B.; Giugliano, D. Mediterranean diet for type 2 diabetes: Cardiometabolic benefits. Endocrine, 2017, 56(1), 27-32.
[http://dx.doi.org/10.1007/s12020-016-1018-2] [PMID: 27395419]
[131]
Samarghandian, S.; Azimi-Nezhad, M.; Samini, F.; Farkhondeh, T. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats. Can. J. Physiol. Pharmacol., 2016, 94(4), 388-393.
[http://dx.doi.org/10.1139/cjpp-2014-0412] [PMID: 26863330]
[132]
Lee, S.P.; Kuo, F.Y.; Cheng, J-T.; Wu, M.C. GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats. Diabetes Metab. Syndr. Obes., 2019, 12, 873-881.
[http://dx.doi.org/10.2147/DMSO.S207596] [PMID: 31354323]
[133]
Hawsawi, Z.A.; Ali, B.A.; Bamosa, A.O. Effect of Nigella sativa (Black Seed) and thymoquinone on blood glucose in albino rats. Ann. Saudi Med., 2001, 21(3-4), 242-244.
[http://dx.doi.org/10.5144/0256-4947.2001.242] [PMID: 17264566]
[134]
Karandrea, S.; Yin, H.; Liang, X.; Slitt, A.L.; Heart, E.A. Thymoquinone ameliorates diabetic phenotype in diet-induced obesity mice via activation of SIRT-1-dependent pathways. PLoS One, 2017, 12(9), e0185374.
[http://dx.doi.org/10.1371/journal.pone.0185374] [PMID: 28950020]
[135]
Fararh, K.M.; Ibrahim, A.K.; Elsonosy, Y.A. Thymoquinone enhances the activities of enzymes related to energy metabolism in periphe-ral leukocytes of diabetic rats. Res. Vet. Sci., 2010, 88(3), 400-404.
[http://dx.doi.org/10.1016/j.rvsc.2009.10.008] [PMID: 19931880]
[136]
Fararh, K.M.; Shimizu, Y.; Shiina, T.; Nikami, H.; Ghanem, M.M.; Takewaki, T. Thymoquinone reduces hepatic glucose production in diabetic hamsters. Res. Vet. Sci., 2005, 79(3), 219-223.
[http://dx.doi.org/10.1016/j.rvsc.2005.01.001] [PMID: 16054891]
[137]
Aljabre, S.H.M.; Randhawa, M.A.; Akhtar, N.; Alakloby, O.M.; Alqurashi, A.M.; Aldossary, A. Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone. J. Ethnopharmacol., 2005, 101(1-3), 116-119.
[http://dx.doi.org/10.1016/j.jep.2005.04.002] [PMID: 15908151]
[138]
Flesar, J.; Havlik, J.; Kloucek, P.; Rada, V.; Titera, D.; Bednar, M.; Stropnicky, M.; Kokoska, L. In vitro growth-inhibitory effect of plant-derived extracts and compounds against Paenibacillus larvae and their acute oral toxicity to adult honey bees. Vet. Microbiol., 2010, 145(1-2), 129-133.
[http://dx.doi.org/10.1016/j.vetmic.2010.03.018] [PMID: 20409652]
[139]
Harzallah, H.J.; Kouidhi, B.; Flamini, G.; Bakhrouf, A.; Mahjoub, T. Chemical composition, antimicrobial potential against cariogenic bac-teria and cytotoxic activity of Tunisian Nigella sativa essential oil and thymoquinone. Food Chem., 2011, 129(4), 1469-1474.
[http://dx.doi.org/10.1016/j.foodchem.2011.05.117]
[140]
Houghton, P.J.; Zarka, R.; de las Heras, B.; Hoult, J.R. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med., 1995, 61(1), 33-36.
[http://dx.doi.org/10.1055/s-2006-957994] [PMID: 7700988]
[141]
Cheng, Q.N.; Yang, X.; Wu, J.F.; Ai, W.B.; Ni, Y.R. Interaction of non parenchymal hepatocytes in the process of hepatic fibrosis (Re-view). Mol. Med. Rep., 2021, 23(5), 364.
[http://dx.doi.org/10.3892/mmr.2021.12003] [PMID: 33760176]
[142]
Saricicek, E.; Tarakcioglu, M.; Saricicek, V.; Gulsen, M.T.; Karakok, M.; Baltaci, Y.; Taysi, S. Effect of Nigella sativa on experimental liver fibrosis. Biomedical Research-India, 2014, 25(1), 32-38.
[143]
Alhebshi, A.H.; Gotoh, M.; Suzuki, I. Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity. Biochem. Biophys. Res. Commun., 2013, 433(4), 362-367.
[http://dx.doi.org/10.1016/j.bbrc.2012.11.139] [PMID: 23537659]
[144]
Daba, M.H.; Abdel-Rahman, M.S. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol. Lett., 1998, 95(1), 23-29.
[http://dx.doi.org/10.1016/S0378-4274(98)00012-5] [PMID: 9650643]
[145]
Brown, C.J.; Cheok, C.F.; Verma, C.S.; Lane, D.P. Reactivation of p53: from peptides to small molecules. Trends Pharmacol. Sci., 2011, 32(1), 53-62.
[http://dx.doi.org/10.1016/j.tips.2010.11.004] [PMID: 21145600]
[146]
Mansour, M.A. Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice. Life Sci., 2000, 66(26), 2583-2591.
[http://dx.doi.org/10.1016/S0024-3205(00)00592-0] [PMID: 10883736]
[147]
Nagi, M.N.; Almakki, H.A. Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: Possible role in protection against chemical carcinogenesis and toxicity. Phytother. Res., 2009, 23(9), 1295-1298.
[http://dx.doi.org/10.1002/ptr.2766] [PMID: 19277968]
[148]
Mabrouk, A.; Bel Hadj Salah, I.; Chaieb, W.; Ben Cheikh, H. Protective effect of thymoquinone against lead-induced hepatic toxicity in rats. Environ. Sci. Pollut. Res. Int., 2016, 23(12), 12206-12215.
[http://dx.doi.org/10.1007/s11356-016-6419-5] [PMID: 26971798]
[149]
Badary, O.A.; Abdel-Naim, A.B.; Abdel-Wahab, M.H.; Hamada, F.M. The influence of thymoquinone on doxorubicin-induced hyperlipi-demic nephropathy in rats. Toxicology, 2000, 143(3), 219-226.
[http://dx.doi.org/10.1016/S0300-483X(99)00179-1] [PMID: 10755708]
[150]
Ragheb, A.; Attia, A.; Elbarbry, F.; Prasad, K.; Shoker, A. Attenuated combined action of cyclosporine A and hyperlipidemia on atheroge-nesis in rabbits by thymoquinone. Evid. Based Complement. Alternat. Med., 2011, 2011, 620319.
[http://dx.doi.org/10.1093/ecam/nep225] [PMID: 20040523]
[151]
Al-Majed, A.A.; Daba, M.H.; Asiri, Y.A.; Al-Shabanah, O.A.; Mostafa, A.A.; El-Kashef, H.A. Thymoquinone-induced relaxation of gui-nea-pig isolated trachea. Res. Commun. Mol. Pathol. Pharmacol., 2001, 110(5-6), 333-345.
[PMID: 12889525]
[152]
Chakravarty, N. Inhibition of histamine release from mast cells by nigellone. Ann. Allergy, 1993, 70(3), 237-242.
[PMID: 7680846]
[153]
El-Abhar, H.S.; Abdallah, D.M.; Saleh, S. Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J. Ethnopharmacol., 2003, 84(2-3), 251-258.
[http://dx.doi.org/10.1016/S0378-8741(02)00324-0] [PMID: 12648823]
[154]
Mahgoub, A.A. Thymoquinone protects against experimental colitis in rats. Toxicol. Lett., 2003, 143(2), 133-143.
[http://dx.doi.org/10.1016/S0378-4274(03)00173-5] [PMID: 12749817]
[155]
Magdy, M.A.; Hanan, A.; Nabila, M. Thymoquinone: Novel gastroprotective mechanisms. Eur. J. Pharmacol., 2012, 697(1-3), 126-131.
[http://dx.doi.org/10.1016/j.ejphar.2012.09.042] [PMID: 23051678]
[156]
Badary, O.A.; Nagi, M.N.; al-Shabanah, O.A.; al-Sawaf, H.A.; al-Sohaibani, M.O.; al-Bekairi, A.M. Thymoquinone ameliorates the nephro-toxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can. J. Physiol. Pharmacol., 1997, 75(12), 1356-1361.
[http://dx.doi.org/10.1139/y97-169] [PMID: 9534946]
[157]
Hadjzadeh, M.A.; Mohammadian, N.; Rahmani, Z.; Rassouli, F.B. Effect of thymoquinone on ethylene glycol-induced kidney calculi in rats. Urol. J., 2008, 5(3), 149-155.
[PMID: 18825620]
[158]
Kanter, M. Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats. Neurochem. Res., 2008, 33(3), 579-588.
[http://dx.doi.org/10.1007/s11064-007-9481-z] [PMID: 17929168]
[159]
Firdaus, F.; Zafeer, M.F.; Waseem, M.; Ullah, R.; Ahmad, M.; Afzal, M. Thymoquinone alleviates arsenic induced hippocampal toxicity and mitochondrial dysfunction by modulating mPTP in Wistar rats. Biomed. Pharmacother., 2018, 102, 1152-1160.
[http://dx.doi.org/10.1016/j.biopha.2018.03.159] [PMID: 29710533]
[160]
Butt, M.S.; Imran, M.; Imran, A.; Arshad, M.S.; Saeed, F.; Gondal, T.A.; Shariati, M.A.; Gilani, S.A.; Tufail, T.; Ahmad, I.; Rind, N.A.; Mahomoodally, M.F.; Islam, S.; Mehmood, Z. Therapeutic perspective of thymoquinone: A mechanistic treatise. Food Sci. Nutr., 2021, 9(3), 1792-1809.
[http://dx.doi.org/10.1002/fsn3.2070] [PMID: 33747489]
[161]
Cascella, M.; Bimonte, S.; Barbieri, A.; Del Vecchio, V.; Muzio, M.R.; Vitale, A.; Benincasa, G.; Ferriello, A.B.; Azzariti, A.; Arra, C.; Cuomo, A. dissecting the potential roles of Nigella sativa and its constituent thymoquinone on the prevention and on the progression of Alzheimer’s disease. Front. Aging Neurosci., 2018, 10, 16.
[http://dx.doi.org/10.3389/fnagi.2018.00016] [PMID: 29479315]
[162]
Radad, K.S.; Al-Shraim, M.M.; Moustafa, M.F.; Rausch, W.D. Neuroprotective role of thymoquinone against 1-methyl-4-phenylpyridinium-induced dopaminergic cell death in primary mesencephalic cell culture. Neurosciences (Riyadh), 2015, 20(1), 10-16.
[PMID: 25630775]
[163]
Khan, A.; Vaibhav, K.; Javed, H.; Khan, M.M.; Tabassum, R.; Ahmed, M.E.; Srivastava, P.; Khuwaja, G.; Islam, F.; Siddiqui, M.S.; Safhi, M.M.; Islam, F. Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress. Mol. Cell. Biochem., 2012, 369(1-2), 55-65.
[http://dx.doi.org/10.1007/s11010-012-1368-x] [PMID: 22752387]
[164]
El Gazzar, M.; El Mezayen, R.; Marecki, J.C.; Nicolls, M.R.; Canastar, A.; Dreskin, S.C. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. Int. Immunopharmacol., 2006, 6(7), 1135-1142.
[http://dx.doi.org/10.1016/j.intimp.2006.02.004] [PMID: 16714217]
[165]
El-Khouly, D.; El-Bakly, W.M.; Awad, A.S.; El-Mesallamy, H.O.; El-Demerdash, E. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats. Toxicology, 2012, 302(2-3), 106-113.
[http://dx.doi.org/10.1016/j.tox.2012.09.001] [PMID: 22982510]
[166]
El Gazzar, M.; El Mezayen, R.; Nicolls, M.R.; Marecki, J.C.; Dreskin, S.C. Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim. Biophys. Acta, 2006, 1760(7), 1088-1095.
[http://dx.doi.org/10.1016/j.bbagen.2006.03.006] [PMID: 16624488]
[167]
Nader, M.A.; el-Agamy, D.S.; Suddek, G.M. Protective effects of propolis and thymoquinone on development of atherosclerosis in cho-lesterol-fed rabbits. Arch. Pharm. Res., 2010, 33(4), 637-643.
[http://dx.doi.org/10.1007/s12272-010-0420-1] [PMID: 20422375]
[168]
Pei, Z.W.; Guo, Y.; Zhu, H.L.; Dong, M.; Zhang, Q.; Wang, F. Thymoquinone protects against hyperlipidemia-induced cardiac damage in Low-Density Lipoprotein Receptor-Deficient (LDL-R-/-) mice via its anti-inflammatory and antipyroptotic effects. BioMed Res. Int., 2020, 2020, 4878704.
[http://dx.doi.org/10.1155/2020/4878704] [PMID: 33178827]
[169]
el Tahir, K.E.; Ashour, M.M.; al-Harbi, M.M. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: Eluci-dation of the mechanism of action. Gen. Pharmacol., 1993, 24(5), 1123-1131.
[http://dx.doi.org/10.1016/0306-3623(93)90359-6] [PMID: 8270171]
[170]
Enomoto, S.; Asano, R.; Iwahori, Y.; Narui, T.; Okada, Y.; Singab, A.N.; Okuyama, T. Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biol. Pharm. Bull., 2001, 24(3), 307-310.
[http://dx.doi.org/10.1248/bpb.24.307] [PMID: 11256491]
[171]
Nagi, M.N.; Al-Shabanah, O.A.; Hafez, M.M.; Sayed-Ahmed, M.M. Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats. J. Biochem. Mol. Toxicol., 2011, 25(3), 135-142.
[http://dx.doi.org/10.1002/jbt.20369] [PMID: 20957680]
[172]
Nagi, M.N.; Mansour, M.A. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: A possible mechanism of protection. Pharmacol. Res., 2000, 41(3), 283-289.
[http://dx.doi.org/10.1006/phrs.1999.0585] [PMID: 10675279]
[173]
al-Shabanah, O.A.; Badary, O.A.; Nagi, M.N.; al-Gharably, N.M.; al-Rikabi, A.C.; al-Bekairi, A.M. Thymoquinone protects against doxo-rubicin-induced cardiotoxicity without compromising its antitumor activity. J. Exp. Clin. Cancer Res., 1998, 17(2), 193-198.
[PMID: 9700580]
[174]
Jin, Y.H.; Cai, L.; Cheng, Z.S.; Cheng, H.; Deng, T.; Fan, Y.P.; Fang, C.; Huang, D.; Huang, L.Q.; Huang, Q.; Han, Y.; Hu, B.; Hu, F.; Li, B.H.; Li, Y.R.; Liang, K.; Lin, L.K.; Luo, L.S.; Ma, J.; Ma, L.L.; Peng, Z.Y.; Pan, Y.B.; Pan, Z.Y.; Ren, X.Q.; Sun, H.M.; Wang, Y.; Wang, Y.Y.; Weng, H.; Wei, C.J.; Wu, D.F.; Xia, J.; Xiong, Y.; Xu, H.B.; Yao, X.M.; Yuan, Y.F.; Ye, T.S.; Zhang, X.C.; Zhang, Y.W.; Zhang, Y.G.; Zhang, H.M.; Zhao, Y.; Zhao, M.J.; Zi, H.; Zeng, X.T.; Wang, Y.Y.; Wang, X.H.; Management, Z.H.W.U.N.C. A rapid advice guide-line for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil. Med. Res., 2020, 7(1), 4.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[175]
Chaieb, K.; Kouidhi, B.; Jrah, H.; Mahdouani, K.; Bakhrouf, A. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation. BMC Complement. Altern. Med., 2011, 11, 29.
[http://dx.doi.org/10.1186/1472-6882-11-29] [PMID: 21489272]
[176]
Akhondian, J.; Kianifar, H.; Raoofziaee, M.; Moayedpour, A.; Toosi, M.B.; Khajedaluee, M. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res., 2011, 93(1), 39-43.
[http://dx.doi.org/10.1016/j.eplepsyres.2010.10.010] [PMID: 21112742]
[177]
Umar, S.; Munir, M.T.; Subhan, S.; Azam, T.; Nisa, Q.; Khan, M.I.; Umar, W.; Rehman, Z.; Saqib, A.S.; Shah, M.A. Protective and antiviral activities of Nigella sativa against avian influenza (H9N2) in turkeys. J. Saudi Soc. Agric. Sci., 2016. Withdrawn article in press.,
[178]
Ulasli, M.; Gurses, S.A.; Bayraktar, R.; Yumrutas, O.; Oztuzcu, S.; Igci, M.; Igci, Y.Z.; Cakmak, E.A.; Arslan, A. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes fa-mily. Mol. Biol. Rep., 2014, 41(3), 1703-1711.
[http://dx.doi.org/10.1007/s11033-014-3019-7] [PMID: 24413991]
[179]
Heinrich, M.; Appendino, G.; Efferth, T.; Fürst, R.; Izzo, A.A.; Kayser, O.; Pezzuto, J.M.; Viljoen, A. Best practice in research - Overco-ming common challenges in phytopharmacological research. J. Ethnopharmacol., 2020, 246, 112230.
[http://dx.doi.org/10.1016/j.jep.2019.112230] [PMID: 31526860]
[180]
Kampan, N.C.; Xiang, S.D.; McNally, O.M.; Stephens, A.N.; Quinn, M.A.; Plebanski, M. Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer: Challenges and opportunities. Curr. Med. Chem., 2018, 25(36), 4785-4806.
[http://dx.doi.org/10.2174/0929867324666170712160621] [PMID: 28707587]
[181]
Luo, P.; Liu, Y.; Qiu, L.; Liu, X.; Liu, D.; Li, J. Tocilizumab treatment in COVID-19: A single center experience. J. Med. Virol., 2020, 92(7), 814-818.
[http://dx.doi.org/10.1002/jmv.25801] [PMID: 32253759]
[182]
Cobourne-Duval, M.K.; Taka, E.; Mendonca, P.; Soliman, K.F.A. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ; -activated BV-2 microglia cells. J. Neuroimmunol., 2018, 320, 87-97.
[http://dx.doi.org/10.1016/j.jneuroim.2018.04.018] [PMID: 29759145]
[183]
Bruce-Hickman, D.; Sajeed, S.M.; Pang, Y.H.; Seow, C.S.; Chen, W.; Gulati Kansal, M. Bowel ulceration following tocilizumab administra-tion in a COVID-19 patient. BMJ Open Gastroenterol., 2020, 7(1), e000484.
[http://dx.doi.org/10.1136/bmjgast-2020-000484] [PMID: 32816957]
[184]
Paoloni-Giacobino, A.; Chen, H.; Peitsch, M.C.; Rossier, C.; Antonarakis, S.E. Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Genomics, 1997, 44(3), 309-320.
[http://dx.doi.org/10.1006/geno.1997.4845] [PMID: 9325052]
[185]
Wilson, S.; Greer, B.; Hooper, J.; Zijlstra, A.; Walker, B.; Quigley, J.; Hawthorne, S. The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. Biochem. J., 2005, 388(Pt 3), 967-972.
[http://dx.doi.org/10.1042/BJ20041066] [PMID: 15537383]
[186]
Matsuyama, S.; Nagata, N.; Shirato, K.; Kawase, M.; Takeda, M.; Taguchi, F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J. Virol., 2010, 84(24), 12658-12664.
[http://dx.doi.org/10.1128/JVI.01542-10] [PMID: 20926566]
[187]
Iwata-Yoshikawa, N.; Okamura, T.; Shimizu, Y.; Hasegawa, H.; Takeda, M.; Nagata, N. TMPRSS2 contributes to virus spread and im-munopathology in the airways of murine models after coronavirus infection. J. Virol., 2019, 93(6), e01815-e01818.
[http://dx.doi.org/10.1128/JVI.01815-18] [PMID: 30626688]
[188]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[189]
Huggins, D.J. Structural analysis of experimental drugs binding to the SARS-CoV-2 target TMPRSS2. J. Mol. Graph. Model., 2020, 100, 107710.
[http://dx.doi.org/10.1016/j.jmgm.2020.107710] [PMID: 32829149]
[190]
Abukhader, M.M. Thymoquinone in the clinical treatment of cancer: Fact or fiction? Pharmacogn. Rev., 2013, 7(14), 117-120.
[http://dx.doi.org/10.4103/0973-7847.120509] [PMID: 24347919]
[191]
Rahmani, A.H.; Alzohairy, M.A.; Khan, M.A.; Aly, S.M. Therapeutic implications of black seed and its constituent thymoquinone in the prevention of cancer through inactivation and activation of molecular pathways. Evid. Based Complement. Alternat. Med., 2014, 2014, 724658.
[http://dx.doi.org/10.1155/2014/724658] [PMID: 24959190]
[192]
Zhang, L.; Bai, Y.; Yang, Y. Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. B. Oncol. Lett., 2016, 12(4), 2840-2845.
[http://dx.doi.org/10.3892/ol.2016.4971] [PMID: 27698868]
[193]
Jafri, S.H.; Glass, J.; Shi, R.; Zhang, S.; Prince, M.; Kleiner-Hancock, H. Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo. J. Exp. Clin. Cancer Res., 2010, 29(1), 87.
[http://dx.doi.org/10.1186/1756-9966-29-87] [PMID: 20594324]
[194]
Reindl, W.; Yuan, J.; Krämer, A.; Strebhardt, K.; Berg, T. Inhibition of polo-like kinase 1 by blocking polo-box domain-dependent pro-tein-protein interactions. Chem. Biol., 2008, 15(5), 459-466.
[http://dx.doi.org/10.1016/j.chembiol.2008.03.013] [PMID: 18482698]
[195]
Strebhardt, K.; Ullrich, A. Targeting polo-like kinase 1 for cancer therapy. Nat. Rev. Cancer, 2006, 6(4), 321-330.
[http://dx.doi.org/10.1038/nrc1841] [PMID: 16557283]
[196]
Wolf, G.; Elez, R.; Doermer, A.; Holtrich, U.; Ackermann, H.; Stutte, H.J.; Altmannsberger, H.M.; Rübsamen-Waigmann, H.; Strebhardt, K. Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer. Oncogene, 1997, 14(5), 543-549.
[http://dx.doi.org/10.1038/sj.onc.1200862] [PMID: 9053852]
[197]
Shanmugam, M.K.; Ahn, K.S.; Hsu, A.; Woo, C.C.; Yuan, Y.; Tan, K.H.B.; Chinnathambi, A.; Alahmadi, T.A.; Alharbi, S.A.; Koh, A.P.F.; Arfuso, F.; Huang, R.Y-J.; Lim, L.H.K.; Sethi, G.; Kumar, A.P. Thymoquinone inhibits bone metastasis of breast cancer cells through abrogation of the CXCR4 signaling axis. Front. Pharmacol., 2018, 9(1294), 1294.
[http://dx.doi.org/10.3389/fphar.2018.01294] [PMID: 30564115]
[198]
Roepke, M.; Diestel, A.; Bajbouj, K.; Walluscheck, D.; Schonfeld, P.; Roessner, A.; Schneider-Stock, R.; Gali-Muhtasib, H. Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol. Ther., 2007, 6(2), 160-169.
[http://dx.doi.org/10.4161/cbt.6.2.3575] [PMID: 17218778]
[199]
Alhosin, M.; Abusnina, A.; Achour, M.; Sharif, T.; Muller, C.; Peluso, J.; Chataigneau, T.; Lugnier, C.; Schini-Kerth, V.B.; Bronner, C.; Fuhrmann, G. Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1. Biochem. Pharmacol., 2010, 79(9), 1251-1260.
[http://dx.doi.org/10.1016/j.bcp.2009.12.015] [PMID: 20026309]
[200]
Wirries, A.; Breyer, S.; Quint, K.; Schobert, R.; Ocker, M. Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells. Exp. Ther. Med., 2010, 1(2), 369-375.
[http://dx.doi.org/10.3892/etm_00000058] [PMID: 22993551]
[201]
Ke, X.; Zhao, Y.; Lu, X.; Wang, Z.; Liu, Y.; Ren, M.; Lu, G.; Zhang, D.; Sun, Z.; Xu, Z.; Song, J.H.; Cheng, Y.; Meltzer, S.J.; He, S. TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling. Oncotarget, 2015, 6(32), 32610-32621.
[http://dx.doi.org/10.18632/oncotarget.5362] [PMID: 26416455]
[202]
Xu, D.; Ma, Y.; Zhao, B.; Li, S.; Zhang, Y.; Pan, S.; Wu, Y.; Wang, J.; Wang, D.; Pan, H.; Liu, L.; Jiang, H. Thymoquinone induces G2/M arrest, inactivates PI3K/Akt and nuclear factor-κB pathways in human cholangiocarcinomas both in vitro and in vivo. Oncol. Rep., 2014, 31(5), 2063-2070.
[http://dx.doi.org/10.3892/or.2014.3059] [PMID: 24603952]
[203]
Sutton, K.M.; Greenshields, A.L.; Hoskin, D.W. Thymoquinone, a bioactive component of black caraway seeds, causes G1 phase cell cycle arrest and apoptosis in triple-negative breast cancer cells with mutant p53. Nutr. Cancer, 2014, 66(3), 408-418.
[http://dx.doi.org/10.1080/01635581.2013.878739] [PMID: 24579801]
[204]
Rajput, S.; Kumar, B.N.; Dey, K.K.; Pal, I.; Parekh, A.; Mandal, M. Molecular targeting of Akt by thymoquinone promotes G(1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci., 2013, 93(21), 783-790.
[http://dx.doi.org/10.1016/j.lfs.2013.09.009] [PMID: 24044882]
[205]
Thabet, N.A.; El-Khouly, D.; Sayed-Ahmed, M.M.; Omran, M.M. Thymoquinone chemosensitizes human colorectal cancer cells to imati-nib via uptake/efflux genes modulation. Clin. Exp. Pharmacol. Physiol., 2021, 48(6), 911-920.
[http://dx.doi.org/10.1111/1440-1681.13476] [PMID: 33783002]
[206]
Joruiz, S.M.; Bourdon, J-C. p53 Isoforms: Key regulators of the cell fate decision. Cold Spring Harb. Perspect. Med., 2016, 6(8), a026039.
[http://dx.doi.org/10.1101/cshperspect.a026039] [PMID: 26801896]
[207]
Muller, P.A.; Vousden, K.H. p53 Mutations in cancer. Nat. Cell Biol., 2013, 15(1), 2-8.
[http://dx.doi.org/10.1038/ncb2641] [PMID: 23263379]
[208]
Meng, X.; Franklin, D.A.; Dong, J.; Zhang, Y. MDM2-p53 pathway in hepatocellular carcinoma. Cancer Res., 2014, 74(24), 7161-7167.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1446] [PMID: 25477334]
[209]
Varanda, E.A.; Tavares, D.C. Radioprotection mechanisms and radioprotective agents including honeybee venom. J. Venom. Anim. Toxins, 1998, 4, 5-21.
[http://dx.doi.org/10.1590/S0104-79301998000100002]
[210]
Alkis, H.; Demir, E.; Taysi, M.R.; Sagir, S.; Taysi, S. Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats. Biomed. Pharmacother., 2021, 139, 111540.
[http://dx.doi.org/10.1016/j.biopha.2021.111540] [PMID: 33831837]
[211]
Lang, D.K.; Singh, H.; Arora, A.; Arora, R.; Saini, B.; Arora, S.; Kaur, R. Radioprotectors: Nature’s Boon. Mini Rev. Med. Chem., 2021.
[http://dx.doi.org/10.2174/1389557521666210120112814] [PMID: 33494677]
[212]
Adnan, M.; Rasul, A.; Shah, M.A.; Hussain, G.; Asrar, M.; Riaza, A.; Sarfraza, I.; Hussaina, A.; Khorsandid, K.; Laie, N.S.; Hussaina, S.M. Radioprotective role of natural polyphenols: From Sources to Mechanisms. Anticancer. Agents Med. Chem., 2022, 22(1), 30-31.
[http://dx.doi.org/10.2174/1871520621666210419095829] [PMID: 33874875]
[213]
Deniz, C.D.; Aktan, M.; Erel, O.; Gurbilek, M.; Koc, M. Evaluation of the radioprotective effects of thymoquinone on dynamic thiol-disulphide homeostasis during total-body irradiation in rats. J. Radiat. Res. (Tokyo), 2019, 60(1), 23-28.
[http://dx.doi.org/10.1093/jrr/rry083] [PMID: 30358876]
[214]
Nagi, M.N.; Almakki, H.A.; Sayed-Ahmed, M.M.; Al-Bekairi, A.M. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem. Toxicol., 2010, 48(8-9), 2361-2365.
[http://dx.doi.org/10.1016/j.fct.2010.05.072] [PMID: 20561950]
[215]
Elgohary, S.; Elkhodiry, A.A.; Amin, N.S.; Stein, U.; El Tayebi, H.M. Thymoquinone: A tie-breaker in SARS-CoV2-infected cancer pa-tients? Cells, 2021, 10(2), 302.
[http://dx.doi.org/10.3390/cells10020302] [PMID: 33540625]
[216]
El-Far, A.H.; Tantawy, M.A.; Al Jaouni, S.K.; Mousa, S.A. Thymoquinone-chemotherapeutic combinations: New regimen to combat can-cer and cancer stem cells. Naunyn Schmiedebergs Arch. Pharmacol., 2020, 393(9), 1581-1598.
[http://dx.doi.org/10.1007/s00210-020-01898-y] [PMID: 32458010]
[217]
Shoieb, A.M.; Elgayyar, M.; Dudrick, P.S.; Bell, J.L.; Tithof, P.K. In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int. J. Oncol., 2003, 22(1), 107-113.
[http://dx.doi.org/10.3892/ijo.22.1.107] [PMID: 12469192]
[218]
Ng, W.K.; Yazan, L.S.; Ismail, M. Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apop-tosis with down-regulation of Bcl-2 protein. Toxicol. In Vitro, 2011, 25(7), 1392-1398.
[http://dx.doi.org/10.1016/j.tiv.2011.04.030] [PMID: 21609759]
[219]
Mansour, M.A.; Ginawi, O.T.; El-Hadiyah, T.; El-Khatib, A.S.; Al-Shabanah, O.A.; Al-Sawaf, H.A. Effects of volatile oil constituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: Evidence for antioxidant effects of thymoquinone. Res. Commun. Mol. Pathol. Pharmacol., 2001, 110(3-4), 239-251.
[PMID: 12760491]
[220]
Badary, O.A.; Al-Shabanah, O.A.; Nagi, M.N.; Al-Bekairi, A.M.; Elmazar, M.M.A. Acute and subchronic toxicity of thymoquinone in mice. Drug Dev. Res., 1998, 44(2-3), 56-61.
[http://dx.doi.org/10.1002/(SICI)1098-2299(199806/07)44:2/3<56:AID-DDR2>3.0.CO;2-9]
[221]
Abukhader, M.M. The effect of route of administration in thymoquinone toxicity in male and female rats. Indian J. Pharm. Sci., 2012, 74(3), 195-200.
[http://dx.doi.org/10.4103/0250-474X.106060] [PMID: 23440704]
[222]
Al-Ali, A.; Alkhawajah, A.A.; Randhawa, M.A.; Shaikh, N.A. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Ni-gella sativa, in mice and rats. J. Ayub Med. Coll. Abbottabad, 2008, 20(2), 25-27.
[PMID: 19385451]
[223]
Khader, M.; Bresgen, N.; Eckl, P.M. in vitro toxicological properties of thymoquinone. Food Chem. Toxicol., 2009, 47(1), 129-133.
[http://dx.doi.org/10.1016/j.fct.2008.10.019] [PMID: 19010375]
[224]
Sarkar, C.; Jamaddar, S.; Islam, T.; Mondal, M.; Islam, M.T.; Mubarak, M.S. Therapeutic perspectives of the black cumin component thymoquinone: A review. Food Funct., 2021, 12(14), 6167-6213.
[http://dx.doi.org/10.1039/D1FO00401H] [PMID: 34085672]

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